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Six patients developed dermatitis while working with ultraviolet curing inks in four different printing plants. Contact allergy was found to the multifunctional acrylate monomers pentaerythritol triacrylate (PETA) and trimethylol propane triacrylate (TMPTA) and to the epoxy acrylate and polyesteracrylate prepolymers.
4 workers developed hand and face dermatitis when exposed to a floor top coat. This contained a polyurethane and a polyfunctional aziridine hardener and additives. The aziridine hardener was made by reacting propyleneimine with a polyfunctional acrylate, trimethylolpropane triacrylate (TMPTA). All 4 reacted to the hardener and to TMPTA, which is present in excess. 2 of them also reacted to pentaerythritol triacrylate (PETA), which can be used in the production of aziridine hardeners. TMPTA and PETA cross-react, and are known sensitizers in UV-hardening acrylates. The present finding shows that well-known sensitizers can be found in hidden sources when used in a quite different chemical process.
To investigate whether esterification of rosin with polyalcohols changes its allergenic potential, abietic acid, the main component of rosin, was esterified with glycerol at high temperature. The major product formed was isolated and identified, using nuclear magnetic resonance (NMR), infra-red (IR) and mass spectrometry (MS) analyses, as glyceryl triabietate (GTA), an ester between one glycerol molecule and 3 abietic acid molecules. According to animal experiments GTA was not allergenic and no cross-reactivity was seen to allergens in unmodified rosin. When testing patients allergic to unmodified rosin, no reactions were found to GTA. Some of the patients reacted to glycerol- and pentaerythritol-esterified rosins. According to HPLC analyses, these esterified rosins still contained unmodified material to which the patients may have reacted. It seems that the esterification of rosin with polyalcohols such as glycerol reduces its allergenic activity, possibly because of the formation of much larger molecules with reduced bioavailability. However, making methyl esters of rosin causes little alteration in the molecular weights of the components and, when unmodified and methylated rosin were tested in patients, we saw no difference between the 2 forms.
This study concerns a 69-year-old female patient with a longstanding history of venous ulcerations on both lower legs and multiple sensitivities, who developed eczematous lesions with the hydrocolloid dressing Combiderm (Convatec Ltd., a Bristol-Myers Squibb division, Ickenham, Middlesex, UK). Epicutaneous tests were positive to this dressing and to a modified colophonium derivative, i.e. glyceryl rosinate, however not to the unmodified colophonium from the standard series. A review of the literature showed several case reports about sensitization to similar hydrocolloids being distributed under various brand names in different countries and which contain the pentaerythritol ester of the hydrogenated rosin as the tackifying agent. Some of the patients described did, while others did not, react to colophonium but only to a modified derivative. In our patient, the reaction to glyceryl rosinate most probably represent cross-sensitivity with the modified colophonium derivative used in Combiderm, the presence (but not the exact nature) of which was showed by the company. In patients where allergic contact dermatitis from hydrocolloid dressings is strongly suspected and colophonium tests negatively, patch testing to modified colophonium derivatives should therefore be performed. As the complete composition of wound dressings is most often unknown, we urgently advocate legal requirements for labelling of those and in fact all medically used devices.
Glycerol trinitrate (GTN) reductase, which enables Agrobacterium radiobacter to utilize GTN and related explosives as sources of nitrogen for growth, was purified and characterized, and its gene was cloned and sequenced. The enzyme was a 39-kDa monomeric protein which catalyzed the NADH-dependent reductive scission of GTN (Km = 23 microM) to glycerol dinitrates (mainly the 1,3-isomer) with a pH optimum of 6.5, a temperature optimum of 35 degrees C, and no dependence on metal ions for activity. It was also active on pentaerythritol tetranitrate (PETN), on isosorbide dinitrate, and, very weakly, on ethyleneglycol dinitrate, but it was inactive on isopropyl nitrate, hexahydro-1,3,5-trinitro-1,3,5-triazine, 2,4,6-trinitrotoluene, ammonium ions, nitrate, or nitrite. The amino acid sequence deduced from the DNA sequence was homologous (42 to 51% identity and 61 to 69% similarity) to those of PETN reductase from Enterobacter cloacae, N-ethylmaleimide reductase from Escherichia coli, morphinone reductase from Pseudomonas putida, and old yellow enzyme from Saccharomyces cerevisiae, placing the GTN reductase in the alpha/beta barrel flavoprotein group of proteins. GTN reductase and PETN reductase were very similar in many respects except in their distinct preferences for NADH and NADPH cofactors, respectively.
Seven workers exposed to ultraviolet printing inks developed contact dermatitis. Six cases were allergic and one irritant. A urethane acrylate resin accounted for five cases of sensitisation, one of which was also sensitive to pentaerythritol triacrylate and another also to an epoxy acrylate resin. One instance of allergy to trimethylpropane triacrylate accounted for the sixth case of contact dermatitis in this group of workers. An irritant reaction is presumed to account for the dermatitis in the individual not proved to have cutaneous allergy by patch tests. In this instance trimethylpropane triacrylate was thought to be the most likely irritating agent. Laboratory investigation proved urethane acrylate to be an allergen. The results of investigations of the sensitisation potentials of urethane acrylate, methylmethacrylate, epoxy acrylate resins, toluene-2,4-diisocyanate, and other multifunctional acrylic monomers in the albino guinea pig are presented. The interpretation of such predictive tests is discussed.
Potassium D-glucose 6-O-[35S]sulfate was partially converted by Tris (greater than or equal 25 mM, pH 7.5) to 35SO4(2-), fructose, and a 35S-labelled compound which was tentatively identified as fructose 6-O-sulfate. The isomerization reaction was also catalyzed by ethanolamine and 2-dimethylaminoethanol but not by glycine, triethanolamine, or pentaerythritol. The significance of these findings in relation to kinetic studies of the enzyme glycosulfatase is discussed.
K-Cl cotransport, the electroneutral-coupled movement of K and Cl ions, plays an important role in regulatory volume decrease. We recently reported that nitrite, a nitric oxide derivative possessing potent vasodilation properties, stimulates K-Cl cotransport in low-K sheep red blood cells (LK SRBCs). We hypothesized that activation of vascular smooth muscle (VSM) K-Cl cotransport by vasodilators decreases VSM tension. Here we tested this hypothesis by comparing the effects of commonly used vasodilators, hydralazine (HYZ), sodium nitroprusside, isosorbide mononitrate, and pentaerythritol, on K-Cl cotransport in LK SRBCs and in primary cultures of rat VSM cells (VSMCs) and of HYZ-induced K-Cl cotransport activation on relaxation of isolated porcine coronary rings. K-Cl cotransport was measured as the Cl-dependent K efflux or Rb influx in the presence and absence of inhibitors for other K/Rb transport pathways. All vasodilators activated K-Cl cotransport in LK SRBCs and HYZ in VSMCs, and this activation was inhibited by calyculin and genistein, two inhibitors of K-Cl cotransport. KT-5823, a specific inhibitor of protein kinase G, abolished the sodium nitroprusside-stimulated K-Cl cotransport in LK SRBCs, suggesting involvement of the cGMP pathway in K-Cl cotransport activation. Hydralazine, in a dose-dependent manner, and sodium nitroprusside relaxed (independently of the endothelium) precontracted arteries when only K-Cl cotransport was operating and other pathways for K/Rb transport, including the Ca-activated K channel, were inhibited. Our findings suggest that K-Cl cotransport may be involved in vasodilation.
It was shown that bismuth(III)hexanoate (Bi(OHex)3) efficiently and selectively catalyzes the addition of tetra(ethylene glycol) (TEG) onto the isocyanate group of 3-isocyanatopropyl triethoxysilane, IPTES. delta-Valerolactone (deltaVL), epsilon-caprolactone (epsilonCL) and D,L-lactide were polymerized by initiation with TEG/Bi(OHex)3. The resulting telechelic polyesters were in situ functionalized with IPTES or with 3-isocyanatopropyl trimethoxysilane, IPTMS. Using pentaerythritol as co-initiator of Bi(OHex)3 and epsilonCL as monomer, star-shaped polylactones having triethylsilyl end-groups were synthesized in a one-pot-procedure. All functionalized polyesters were characterized by 1H-NMR and 13C-NMR spectroscopy and by MALDI-TOF mass spectrometry. Bi(OHex)3 is a remarkable initiator and catalyst, because of its extraordinary low toxicity.
The purpose of this paper is to show, by noninvasive measurements, previously undocumented effects on cardiac work of the nitrate coronary vasodilator Pentaerythritol Tetranitrate (Peritrate). The chew-and-swallow 40-mg tablets of this drug were given to 10 patients of type II AHA classification. The Diastolic Time Tension Index/Systolic Time Tension Index Ratio increased significantly from 1.15 (+/- 0.11 SEM) to 1.46 (+/- 0.13), p less than 0.05. The Double Product decreased significantly from 9813 (+/- 606) to 8336 (+/- 497), p less than 0.01. The Triple Product also decreased significantly from 3223 (+/- 235) to 2425 (+/- 206), p less than 0.01. The percent diastole of the R-R interval increased significantly from 65% (+/- 2.44) to 70% (+/- 1.73) p less than 0.05, while no significant change in heart rate occurred (63.2 bts/min to 62.4 bts/min). Correspondingly, there was a decrease of systolic time interval, from 0.33 second (+/- 0.2) to 0.29 second (+/- .01) p less than 0.01. A significant decrease in blood pressure was also noted. Systolic BP dropped from 155 (+/- 8.0) to 134 (+/- 7.2), p less than 0.01. Diastolic BP dropped from 89.2 (+/- 2.8) to 79.2 (+/- 2.2), p less than 0.01. This study shows that Peritrate produced significantly favorable changes in all the cited indicators of cardiac work.
The film forming and coating properties of Glycerol ester of maleic rosin (GMR) and Pentaerythritol ester of maleic rosin (PMR) were investigated. The 2 rosin-based biomaterials were initially characterized in terms of their physicochemical properties, molecular weight (Mw), and glass transition temperature (Tg). Films were produced by solvent evaporation technique on a mercury substrate. Dibutyl sebacate plasticized and nonplasticized films were characterized by mechanical (tensile zzzz strength, percentage elongation, and Young's modulus), water vapor transmission (WVT), and moisture absorption parameters. Plasticization was found to increase film elongation and decrease the Young's modulus, making the films more flexible and thereby reducing the brittleness. Poor rates of WVT and percentage moisture absorption were demonstrated by various film formulations. Diclofenac sodium-layered pellets coated with GMR and PMR film formulations showed sustained drug release for up to 10 hours. The release rate was influenced by the extent of plasticization and coating level. The results obtained in the study demonstrate the utility of novel rosin-based biomaterials for pharmaceutical coating and sustained-release drug delivery systems.
Using the gene mapping membrane technique, we identified a gene (nemA) that encodes N-ethylmaleimide reductase in Escherichia coli. The open reading frame encodes a polypeptide of 365 amino acids with a molecular mass of 39,514 Da. The deduced amino acid sequence showed a high degree of homology (87% identical) with the pentaerythritol tetranitrate reductase of Enterobacter cloacae and the morphinone reductase of Pseudomonas putida (52% identical).
The effects of organic nitrates on tone and tissue cyclic nucleotide levels were studied, using canine coronary, mesenteric and renal arteries, and femoral veins. Glyceryl trinitrate (GTN) relaxed all vascular tissues examined and increased tissue cyclic GMP (cGMP) levels in a concentration-dependent manner, but GTN induced no significant changes in cyclic AMP (cAMP) levels. An increase in cGMP levels induced by 10 microM of GTN in coronary arteries was observed before the onset of relaxation. Methylene blue, an inhibitor of guanylate cyclase, inhibited the relaxant effect of GTN and decreased cGMP levels. In contrast, M & B 22,948, an inhibitor of cGMP phosphodiesterase, not only enhanced relaxation by GTN, but also increased cGMP levels. Other organic nitrates, pentaerythritol tetranitrate (PETN), nicorandil (NIC), and isosorbide dinitrate (ISDN), also relaxed coronary arteries and increased cGMP levels in a concentration-dependent manner. A significant correlation was observed between percentage increases in cGMP levels and percentage relaxation by 10 microM of GTN, PETN, NIC, and ISDN (r = 0.952, p less than 0.001). Plasma concentrations of 4 organic nitrates inversely correlated with percentage increases in cGMP levels by 10 microM of these agents in coronary arteries (r = -0.845, p less than 0.001). These results suggest that an increase in cGMP is responsible for relaxation in vascular smooth muscles by organic nitrates, and that therapeutic plasma concentrations may be estimated by the degree of increase in cGMP levels induced by their administration.
Atherosclerotic lesions were formed in the aorta of rats given a high cholesterol diet containing propylthiouracil (PTU) and vitamin D2 (atherogenic diet) for 8 weeks. The effects of niceritrol (pentaerythritol tetranicotinate), which lower the plasma lipid level, on lipid metabolism in the arterial wall of the atherosclerotic rats were studied. Niceritrol significantly decreased the plasma cholesterol level of atherosclerotic rats, which was 823 mg/100 ml, or about ten times that of control rats. On treatment with niceritrol, the cholesterol level was reduced most in the very low density lipoprotein (VLDL) fraction (d less than 1.006). Heparin-releasable lipoprotein lipase activity in epididymal adipose tissue, lipoprotein lipase activity in post-heparin plasma, and VLDL-triolein hydrolyzing activity in adipose tissue stromal vessels were all higher in niceritrol-treated atherosclerotic rats. Of the enzymes in the arterial wall concerned with cholesterol ester metabolism, acid cholesterol esterase activity was decreased in atherosclerotic rats, while niceritrol treatment increased this activity. The ratio of acyl-CoA cholesterol acyltransferase activity (ACAT) to neutral cholesterol esterase activity was higher in atherosclerotic rats than in control rats, but was lower in niceritrol-treated rats than in atherosclerotic rats. From these results, it is concluded that niceritrol modifies enzyme activities in such a way as to reduce the cholesterol ester content of the arterial wall and lower plasma VLDL and LDL cholesterol levels.
BACKGROUND/AIM: A comprehensive reform strategy in drug management has been applying for a few years in Montenegro in order to promote a rational use of drugs. The reform strategy covered: an information system named "The Control of Distribution and Use of Drugs", a new List of Essential Drugs (that are reimbursed by the Republic Fund for Health), legislative and regulatory measures in order to establish a better control of drug prescribing and more efficient processing of the prescriptions. The aim of this study was to evaluate the effects of the reform strategy on the doctors' prescribing habits and the subsequent use of cardiovascular drugs within the outpatient setting of Montenegro. METHODS: A retrospective-prospective pharmacoepidemiologic study included a sample of 100% of cardiovascular drugs that were taken with prescription from state pharmacies during 2000 and 2004. The results were presented by the number of defined daily doses (DDD) per 1000 inhabitants per day. All the drugs were classified according to the uniform anatomical-therapeutic-chemical (ATC) classification of the drugs. The Wilcoxon test for matched pairs was used in order to calculate the significance of difference in cardiovascular drugs utilization before and after the introduction of new measures. RESULTS: Although prescribing and the resulting outpatient use of cardiovascular drugs (ATC group C) that were reimbursed by the Republic Fund for Health was increased approximately by 13% in 2004 in comparison with 2000 (67.98 vs. 60.17 DDD/1000 inh./day), we did not find a statistically significant difference (p > 0.05). Prescribing of ACE inhibitors (C09A) increased approximately by 45% during the investigated period (15.30 vs. 22.17 DDD/1000 inh./day). The selection of drugs was also altered: cilazapril, ramipril and quinapril were left out, captopril and enalapril were more prescribed, and a newly-induded fosinopril was prescribed mostly (31.5%). Calcium-channel blockers (C08) were prescribed 33.7% more (7.12 vs. 9.52 DDD/1000 inh./day), mostly because of seven times higher prescribing of amlodipine in 2004. Pentaerythritol tetranitrate was left out, but isosorbide dinitrate and isosorbide mononitrate were prescribed more frequently. High-priced atorvastatin was replaced with the older simvastatin, that was prescribed three times more. CONCLUSION: The reform strategy in drug management mostly improved the doctors' prescribing habits and the subsequent use of cardiovascular drugs within the outpatient setting. For the most part, the noticed changes were in accordance with the actual recommendations, but some cases need additional measures. Regulatory policy, however, could not compensate for the continual education of doctors that prescribe drugs.
A case of disseminated allergic contact dermatitis in a screen process printer is presented. The skin lesions were caused by multifunctional acrylates (methylpropane triacrylate and pentaerythritol triacrylate--highly positive patch tests (+ + +) after 48 and 96 h) present in ultraviolet cured transparent lacquer used in coat printed posters to make them weather-resistant. Patch tests with lacquer were also highly positive (+ + +) after 48 and 96 h. According to the safety sheet of the product, lacquer contained 85-90% of multifunctional acrylates. The patient showed disseminated dermatitis, however, no hypertrophied lesions on the hand skin, a characteristic symptom in persons exposed to acrylates, were observed.
1. A baseline toxicity QSAR model was derived for the 24-h LC50 to the goldfish, Carassius auratus. 2. The QSAR-predicted LC50 values for six epoxide derivatives were 2.8-985 times greater than measured. The excess toxicity of these epoxides and other compounds was ascribed to an electrophile molecular mechanism involving SN2 reaction with sulphydryl and other neucleophile groups present in enzymes and other biological macromolecules. 3. The excess toxicities of allyl alcohol and pentaerythritol triallyl ether were interpreted in terms of proelectrophile mechanisms. For the latter compound, this involves a monooxygenase-mediated free radical proton abstraction to a stable allyl radical. The allyl-free radical can undergo enzymic free radical hydroxylation to afford the corresponding acetal, which on decomposition yields the Michael acceptor electrophile acrolein.
Rosin and rosin esters have excellent film-forming properties. Pentaerythritol-rosin ester (penta-ester gum) is found to be useful as moisture-protecting material with delayed release of drug. This communication relates the effect of pH on the release characteristics of a drug from penta-ester gum coated microcapsules. Salicylic acid granules were encapsulated using a 10 per cent solution of penta-ester gum in acetone. The microcapsules were evaluated for their drug release characteristics. Various pH media (pH 1.2, 3.0, 5.0, 7.2 and 8.0) were used. The results showed that penta-ester gum exhibits excellent resistance to higher pH levels and can be used for the sustained release of the drug. Dissolution rate constants were calculated and they agree with the assumption of Hixson and Crowell's cube-root equation.